The use of carbohydrate and peptide antigens in vaccines is greatly hampered by their lack of immunogenicity when injected directly into a patient. Such antigens, when injected alone, are usually ignored by antigen-presenting cells (APCs), cleared rapidly and do not induce an immune response.
In most cases, it is also necessary to administer the antigen in combination with an adjuvant. The adjuvant may be a simple delivery system such as liposomes, which slow clearance of the antigen and make it more likely to reach and be taken up by APCs. However, this in itself is not very effective and usually needs to be combined with agents that stimulate the immune system, such as bacterial products which stimulate cytokine formation. Cytokines themselves may also be co-administered. Many of these products are too toxic or too experimental to be used in humans, and the most effective adjuvants are not approved for human use. Most of the adjuvants available for use in humans are of limited effectiveness. Finding effective adjuvants suitable for human use is a continuing challenge.
Carbohydrate antigens are of particularly weak immunogenicity because they can stimulate only B-cell and not T-cell responses. This is usually circumvented by conjugating the carbohydrate to a protein carrier. However, in order to raise an immune response it is also necessary to use an adjuvant.
Many bacteria and other pathogens are also distinguished by carbohydrate antigens which would be a good target for vaccines, if carbohydrates were not so poorly immunogenic. Improving the immunogenicity of carbohydrate antigens would thus have applications in a wide variety of therapeutic fields.
WO 02/32404 (Consejo Superior de Investigaciones Cientificas) discloses nanoparticles formed from metal or semiconductor atoms in which ligands comprising carbohydrates are covalently linked to the core of the nanoparticles. These nanoparticles are used for modulating carbohydrate mediated interactions and are soluble and non-toxic. WO 2004/108165 (Consejo Superior de Investigaciones Cientificas and Midatech Limited) discloses magnetic nanoparticles having cores comprising passive and magnetic metal atoms, the core being covalently linked to ligands. WO 2005/116226 (Consejo Superior de Investigaciones Cientificas and Midatech Limited) discloses nanoparticles which are conjugated to RNA ligands, in particular siRNA ligands.
There remains a continuing need in the art for ways of delivering antigens to patients to vaccinate them against infection by pathogenic organisms such as bacteria, viruses and parasites. In particular, vaccines often require multiple doses to be administered to individuals to provide adequate protection against infection and contain peptide or protein antigens that are difficult to formulate in stable compositions, especially where the vaccines need to be stored and used in difficult environments.